CHEMICAL SCREENS FOR NEW INDUCERS OF FETAL HEMOGLOBIN (SBIR/STTR)
RELEASE DATE: December 30, 2002
PA NUMBER: PA-03-049
EXPIRATION DATE: December 1, 2005, unless reissued
APPLICATION RECEIPT DATES: Applications submitted in response to this PA
will be accepted on the standard SBIR/STTR application deadlines (April 1,
August 1, and December 1).
National Heart, Lung, and Blood Institute (NHLBI)
(http://www.nhlbi.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov)
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
The National Heart, Lung, and Blood Institute (NHLBI) and the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite grant
applications for Small Business Innovation Research (SBIR) and Small Business
Technology Transfer (STTR) awards to support research and development of new
drugs to increase fetal hemoglobin levels for the treatment of beta-chain
hemoglobinopathies such as sickle cell disease (SCD) and Cooley's anemia (CA;
beta-thalassemia). The goal of this Program Announcement (PA)is to encourage
the use of SBIR and STTR mechanisms to support new chemical activity screens
and drug design efforts for new pharmacologic inducers of fetal hemoglobin.
The ultimate long-term objective will be to bring new fetal hemoglobin
inducers to clinical practice to improve upon drugs such as hydroxyurea, the
only FDA-approved drug for treatment of sickle cell disease. Hydroxyurea is
thought to work in part through fetal hemoglobin induction, but does not
benefit all patients. It is well established that SCD and CA can be cured
with adequate reactivation of endogenous fetal hemoglobin genes silenced
during development. Initial drug activity screens that are high-throughput in
nature are encouraged. These screens should include but not be limited to
compounds in the short chain fatty acid and carbonic acid classes, which have
shown great promise in this area. As commercial activity in this area has
decreased significantly in the last decade, it is hoped that this PA will
stimulate and renew interest within the small business community to develop
new pharmacologic and/or combined pharmacologic-genetic approaches to fetal
hemoglobin induction, to cure SCD and CA.
RESEARCH OBJECTIVES
Background
Since the late 1970s, strong epidemiologic evidence has been gathered that
shows high levels of fetal hemoglobin are curative for SCD and CA. Over the
last two decades, this knowledge has provided a strong rationale to search
for drugs that modify expression of fetal hemoglobin. Historically,
pharmacologic induction of fetal hemoglobin has been attempted with two
approaches. One is the use of cytotoxic drugs. This method is based on the
observation that production of fetal hemoglobin can be stimulated by rapid
regeneration of erythropoiesis. Cytotoxic drugs produce rapid erythroid
regeneration following the killing of cycling hematopoietic cells. The
induction of fetal hemoglobin by hydroxyurea, currently approved for
treatment of SCD patients in acute vaso-occlusive crisis, is based on that
principle (though it has still not been conclusively proven that the
therapeutic effect of hydroxyurea is mediated through fetal hemoglobin
induction). Significant variation in the level of induction of fetal
hemoglobin synthesis is characteristic of treatment with hydroxyurea, and in
about one-third of patients this treatment is ineffective. Furthermore,
hydroxyurea (and other cytotoxic drugs) are ineffective in severe homozygous
CA and they are only slightly effective in intermediate severity CA. The
second approach is the induction of fetal hemoglobin by compounds that most
likely act at the level of chromatin. Two types of compounds fall in this
category: 5-azacytidine, and short chain fatty acids. 5-azacytidine
stimulates fetal hemoglobin synthesis by affecting the level of DNA
methylation and indirectly increasing fetal hemoglobin gene transcription by
modulating DNA/protein interactions and chromatin remodeling. Short chain
fatty acids probably act by increasing the level of chromatin acetylation
because of inhibition of the activity of histone deacetylase. 5-azacytidine
induces fetal hemoglobin in patients with SCD and CA, but its clinical use is
very limited because this compound is considered to be carcinogenic.
Butyrate induces fetal hemoglobin in patients with SCD and CA, but the
therapeutic usefulness of this treatment is limited by the need of
administration of this drug through intravenous infusions that last for
several hours.
A significant development of the last ten years has been the realization that
the potential of induction of fetal hemoglobin synthesis is shared by a large
number of compounds. Thus, all short chain fatty acids with 2-9 carbon atoms,
as well as short chain fatty acid derivatives and analogues have been shown
to act as fetal hemoglobin inducers. Other categories of organic chemicals
have shown to have this property in vitro or in vivo. These findings permit
the prediction that potent inducers of fetal hemoglobin synthesis can be
discovered through empirical screening of chemicals. Thus, there is solid
clinical, cell biological and biochemical evidence that the induction of
fetal hemoglobin can cure SCD and CA, and there is proof of principle that
fetal hemoglobin can be induced with pharmacological means, but there are
severe limitations to the effectiveness of the currently used fetal
hemoglobin inducers. It is therefore necessary to launch a focused research
effort to discover new approaches for therapeutic induction of fetal
hemoglobin synthesis. Compounds that can be taken orally and are effective in
both SCD and CA are required.
This PA encourages the use of the National Institutes of Health (NIH) SBIR
and STTR grant mechanisms to explore various approaches to high-throughput
screening of synthetic chemical or natural product libraries, to identify new
drugs with fetal hemoglobin induction activity and develop them for clinical
application (e.g. file an Investigational New Drug application with the FDA,
and carry out Phase I-III clinical trials). The NHLBI has supported through a
cooperative agreement since 1997 a Reference Laboratory to Evaluate New
Therapies for Sickle Cell Disease, that is located at the Children's Hospital
of Philadelphia and that carries out small-scale drug screening for fetal
hemoglobin inducers. Applicants planning to respond to this PA are encouraged
to consult with this Reference Laboratory before preparing an application
(contact NHLBI Program representative listed below). In addition, the NHLBI
and NIDDK are co-sponsoring an active Request for Applications(RFA) on
transactivation of fetal hemoglobin genes, and the NHLBI is soon to sponsor a
second RFA on fetal hemoglobin gene silencing. Grantees funded in response to
this PA are encouraged to attend the joint RFA investigator meetings to be
held for these two RFAs in the Fall (contact NHLBI Program representative
listed below for details). It is expected that the high-throughput initial
screening portion of this research will be carried out primarily, but not
exclusively using in vitro cell culture systems. Toxicology studies,
pharmacokinetic, and late stage efficacy studies may be carried out in rodent
models engineered to contain a human fetal hemoglobin gene, and/or in large
animal models (e.g. non-human primates).
Research Goals and Topics
The following research areas are examples of appropriate topics for
applications in response to this PA. This list is meant to be representative
and not all-inclusive:
o Develop new automated, high-throughput assays or chemical activity screens
for classical drug discovery efforts based on fetal hemoglobin induction
activity. Assay methods that employ robotics, and that are physiologically
relevant are needed.
o Screen synthetic or natural product chemical libraries of high complexity
for fetal hemoglobin induction activity using new or existing rapid assays.
The application of new assay methods to existing chemical libraries published
in the scientific literature is encouraged. New chemical libraries with well-
documented diversity and complexity may also be useful.
o Screen synthetic or natural product chemical libraries of low complexity
and limited to compounds in the short chain fatty acid and carbonic acid
classes (many examples of which are known to possess fetal hemoglobin
induction activity).
o Using rational drug design, study, refine, and optimize the structure-
activity relationships of candidate fetal hemoglobin-inducing drugs
identified in initial screens.
o Develop genetic approaches to drug discovery focused on fetal hemoglobin
induction. Methods that might be employed include the construction and
screening of artificial transcription factors that activate gamma-globin,
interfering RNAs (RNAi), or catalytic RNAs, all coupled with gene transfer
methods.
o Pursue signal transduction pathway-based drug discovery for fetal
hemoglobin inducers by screening for drugs that modify or modulate the
activity of specific regulatory proteins known to participate in the
activation of fetal hemoglobin expression.
o Advance to large animal studies candidate inducers of fetal hemoglobin that
have shown promise in vitro, and/or in small animal studies.
o Advance to clinical studies in hemoglobinopathy subjects inducers that have
shown promise in large animal studies or prior pilot clinical studies.
o Develop genetic or pharmacologic means to specifically inhibit the gamma-
globin gene silencing that occurs in the neonatal period of human
development. Therapeutic agents developed from such approaches could
potentially be used for treatment of newborns diagnosed with homozygous
sickle cell disease or Cooley's anemia, in order to inhibit the gamma- to
beta-globin gene switch and thus continue synthesis of fetal hemoglobin into
infancy. Either genetic or non-genetic approaches may be feasible.
o Develop pharmacologic or genetic means to inhibit the gamma-globin gene
silencing that takes place during the process of maturation of adult
erythroid progenitors.
o Use combined pharmacologic-genetic approaches to fetal hemoglobin
induction.
MECHANISM OF SUPPORT SBIR AND STTR
This PA will use the NIH Small Business Innovation Research (SBIR) and Small
Business Technology Transfer (STTR) award mechanisms. As an applicant, you
will be solely responsible for planning, directing, and executing the
proposed project.
Except as otherwise stated in this PA, awards will be administered under NIH
grants policy as stated in the NIH Grants Policy Statement, March 2001,
available at http://grants.nih.gov/grants/policy/nihgps_2001.
Applications can be submitted for support as Phase I STTR (R41) or Phase I
SBIR (R43) grants; or under the SBIR/STTR FAST-TRACK option as described in
the SBIR/STTR Omnibus Solicitation. Phase II applications in response to this
PA will only be accepted as competing continuations of previously funded NIH
Phase I SBIR/STTR awards. The Phase II proposal must be a logical extension
of the Phase I research.
ELIGIBLE INSTITUTIONS
Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.
Small business concerns are eligible to submit applications. A small business
concern is one that, on the date of award for both Phase I and Phase II
agreements, meets all of the following criteria:
o is organized for profit, with a place of business located in the United
States, which operates primarily within the United States or which makes a
significant contribution to the United States economy through payment of
taxes or use of American products, materials, or labor;
o is in the legal form of an individual proprietorship, partnership, limited
liability company, corporation, joint venture, association, trust or
cooperative, except that where the form is a joint venture (as defined in
this section) there can be no more than 49 percent participation by foreign
business entities in the joint venture;
o is at least 51 percent owned and controlled by one or more individuals who
are citizens of, or permanent resident aliens in, the United States; has,
including its affiliates, not more than 500 employees, and meets the other
regulatory requirements found in 13 CFR Part 121. Business concerns, other
than investment companies licensed, or state development companies qualifying
under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are
affiliates of one another when either directly or indirectly, (a) one concern
controls or has the power to control the other; or (b) a third party/parties
controls or has the power to control both. Control can be exercised through
common ownership, common management, and contractual relationships. The term
"affiliates" is defined in greater detail in 13 CFR 121.3-2(a). The term
"number of employees" is defined in 13 CFR 121.3-2(t).
Business concerns include, but are not limited to, any individual (sole
proprietorship), partnership, corporation, joint venture, association, or
cooperative. Further information may be obtained by contacting the Small
Business Administration Size District Office at http://www.sba.gov/size/. For
both Phase I and Phase II, the R&D must be performed in its entirety in the
United States. For both Phase I and Phase II, the proposed work must be
performed in its entirety in the United States.
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage your inquiries concerning this PA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research and financial or grants management issues:
o Direct your questions about scientific/research issues to:
Pankaj Qasba, Ph.D.
Blood Diseases Program
National Heart Lung and Blood Institute
6701 Rockledge Dr, MSC 7950
Bethesda MD 20892-7950
Telephone: 301-435-0050
Fax: 301-480-0868
Email: qasbap@nhlbi.nih.gov
David G. Badman, Ph.D.
Hematology Program Director
Deputy Director for Basic Program Administration
DKUHD, NIDDK, NIH
2 Democracy Plaza, Room 621 MSC 5458
6707 Democracy Blvd.
Bethesda, MD 20892-5458
Telephone: 301-594-7717
Fax: 301-480-3510
Email: db70f@nih.gov
o Direct your questions about financial or grants management matters to:
Shelia Ortiz
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Dr, MSC 7926
Bethesda MD 20892-7926
Telephone: 301-435-0166
Fax: 301-480-3310
Email: ortizs@nhlbi.nih.gov
SUBMITTING AN APPLICATION
The PHS 398 research grant application (rev. 5/2001) must be used for all
Phase I, Phase II and Fast-Track applications (new and revised.)
Instructions and forms are available at
http://grants.nih.gov/grants/funding/phs398/phs398.html. Prepare your
application in accordance with the SBIR/STTR Omnibus Solicitation and Chapter
VI of the PHS 398. The NIH will return applications that are not submitted on
the 5/2001 version of the PHS 398. For further assistance contact
GrantsInfo, Telephone: (301) 710-0267, Email:GrantsInfo@nih.gov.
SPECIFIC INSTRUCTIONS FOR PHASE I APPLICATIONS: Application forms,
requirements, and procedures are the same as listed in the Omnibus
Solicitation for Phase I SBIR/STTR Grant applications
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf), except for the
following:
o Type the title and number of this PA on line 2 on the face page of the
application.
o The Omnibus Solicitation states levels for Phase I and Phase II budgets
that are guidelines, not ceilings. SBIR applications requesting up to
$100,000 in total costs (direct costs, indirect costs, and fee) must be
submitted in a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level of
budgetary detail. Section VI of the research grant application instructions
for the PHS 398 at
http://grants.nih.gov/grants/funding/phs398/instructions2/p1_preparing
_SBIR_STTR_app.htm includes
step-by-step guidance for preparing modular grants. Additional information on
SBIR modular grants is available at
http://grants.nih.gov/grants/funding/phs398/instructions2/p1_SBIRSTTR
_general_instructions.htm.
Applications for over $100,000 total costs must include a detailed budget and
budget justification (Form Pages 4 and 5).
SPECIFIC INSTRUCTIONS FOR Phase II Applications: Phase II applications will
be accepted only as competing continuations of previously funded NIH Phase I
SBIR or STTR awards. The Phase II application must be for developmental work
that is a logical extension of the feasibility research conducted during
Phase I. When preparing an application for a Phase II award, you should
follow the instructions for NIH Phase II SBIR or STTR applications. The
instructions and forms for a Phase II SBIR and STTR award are available at
http://grants.nih.gov/grants/funding/phs398/phs398.html.
SPECIFIC INSTRUCTIONS FOR FAST TRACK APPLICATIONS: The NIH Fast-Track
mechanism expedites the decision and award of SBIR and STTR Phase II funding
for scientifically meritorious applications that have a high potential for
commercialization. Fast Track incorporates a submission and review process,
in which complete Phase I and Phase II grant applications are submitted
simultaneously and reviewed together. The FAST-TRACK must have a section
labeled Milestones at the end of the Phase I Research Plan. This section must
include well-defined quantifiable milestones for completion of Phase I, a
discussion of the suitability of the proposed milestones for assessing the
success in Phase I, and a discussion of the implications of successful
completion of these milestones on the proposed Phase II. Failure to provide
such information in the Phase I application and/or sufficient detail in the
Phase II application may be sufficient reason for the peer review committee
to exclude the Phase II from consideration. If so, the applicant may apply
later for Phase II support. Such applications will be reviewed by an
appropriate scientific review group convened by the NIH.
In addition, the Phase II portion of a Fast Track application must include a
concise Commercialization Plan (Product Development Plan), which is limited
to ten pages. Label this section clearly and include it in Section J of the
Phase II Research Plan. More detailed instructions on the preparation of a
Fast Track application are described in the PHS 398 at
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf#page=21.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the checklist, and five signed photocopies in one
package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE CENTER FOR SCIENTIFIC
REVIEW WILL NO LONGER BE ACCEPTED. This policy does not apply to
courier deliveries (i.e. FEDEX, UPS, DHL, etc.)
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-012.html)
APPLICATION PROCESSING: Applications must be received by or mailed on or
before the receipt dates described above.
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will
not accept any application in response to this PA that is essentially the
same as one currently pending initial review unless the applicant withdraws
the pending application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude the
submission of a substantial revision of an application already reviewed, but
such application must include an Introduction addressing the previous
critique.
PEER REVIEW PROCESS
Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
convened in accordance with the standard NIH peer review procedures
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific
and technical merit.
As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a second level review by the National Heart, Lung and Blood
Advisory Council and the National Diabetes and Digestive and Kidney Diseases
Advisory Council.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to discuss the following
aspects of your application in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of these
goals:
o Significance
o Approach
o Innovation
o Investigator
o Milestones and Proof of Principle
o Environment
The scientific review group will address and consider each of these criteria
in assigning your application's overall score, weighting them as appropriate
for each application. Your application does not need to be strong in all
categories to be judged likely to have major scientific impact and thus
deserve a high priority score. For example, you may propose to carry out
important work that by its nature is not innovative but is essential to move
a field forward.
ALL SBIR/STTR APPLICATIONS
1. Significance: Does the proposed project have commercial potential to
lead to a marketable product or process? Does this study address an
important problem? What may be the anticipated commercial and societal
benefits of the proposed activity? If the aims of the application are
achieved, how will scientific knowledge be advanced? Does the proposal
lead to enabling technologies (e.g., instrumentation, software) for
further discoveries? Will the technology have a competitive advantage
over existing/alternate technologies that can meet the market needs?
2. Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of
the project? Is the proposed plan a sound approach for establishing
technical and commercial feasibility? Does the applicant acknowledge
potential problem areas and consider alternative strategies? Are the
milestones and evaluation procedures appropriate?
3. Innovation: Does the project challenge existing paradigms or employ
novel technologies, approaches or methodologies? Are the aims original
and innovative?
4. Investigators: Is the Principal Investigator capable of coordinating
and managing the proposed SBIR/STTR? Is the work proposed appropriate
to the experience level of the Principal Investigator and other
researchers, including consultants and subcontractors (if any)? Are the
relationships of the key personnel to the small business and to other
institutions appropriate for the work proposed?
5. Environment : Is there sufficient access to resources (e.g.,
equipment, facilities)? Does the scientific and technological
environment in which the work will be done contribute to the
probability of success? Do the proposed experiments take advantage of
unique features of the scientific environment or employ useful
collaborative arrangements?
In accordance with NIH policy, the following criteria will be applied to ALL
applications:
Budget: For all applications, is the percent effort listed for the PI
appropriate for the work proposed? On applications requesting up to $100,000
total costs, is the overall budget realistic and justified in terms of the
aims and methods proposed? On applications requesting over $100,000 in total
costs, is each budget category realistic and justified in terms of the aims
and methods?
Human Subjects:
1. Protection of Human Subjects from Research Risks - for all studies
involving human subjects. See instructions and "Guidance for Preparing
the Human Subjects Research Section."
If an exemption is claimed, is it appropriate for the work proposed? If
no exemption is claimed, are the applicant's responses to the six
required points appropriate?
Are human subjects placed at risk by the proposed study? If so, are the
risks reasonable in relation to the anticipated benefits to the
subjects and others? Are the risks reasonable in relation to the
importance of the knowledge that reasonably may be expected to be
gained?
Are the plans proposed for the protection of human subjects adequate?
2. Inclusion of Women Plan - for clinical research only. Does the
applicant propose a plan for the inclusion of both genders that will
provide their appropriate representation? Does the applicant provide
appropriate justification when representation is limited or absent?
Does the applicant propose appropriate and acceptable plans for
recruitment/outreach and retention of study participants?
3. Inclusion of Minorities Plan - for clinical research only . Does the
applicant propose a plan for the inclusion of minorities that will
provide their appropriate representation? Does the applicant provide
appropriate justification when representation is limited or absent?
Does the applicant propose appropriate and acceptable plans for
recruitment/outreach and retention of study participants?
4. Inclusion of Children Plan- for all studies involving human subjects .
Does the applicant describe an acceptable plan in which the
representation of children of all ages (under the age of 21) is
scientifically appropriate and recruitment/retention is addressed
realistically? If not, does the applicant provide an appropriate
justification for their exclusion?
5. Data and Safety Monitoring Plan for clinical trials only . Does the
applicant describe a Data and Safety Monitoring Plan that defines the
general structure of the monitoring entity and mechanisms for reporting
Adverse Events to the NIH and the IRB?
Animal Welfare: If vertebrate animals are involved, are adequate plans
proposed for their care and use? Are the applicant's responses to the five
required points appropriate? Will the procedures be limited to those that are
unavoidable in the conduct of scientifically sound research?
Biohazards: Is the use of materials or procedures that are potentially
hazardous to research personnel and/or the environment proposed? Is the
proposed protection adequate?
Phase II Application Review Criteria: In addition to the above criteria:
1. How well did the applicant demonstrate progress toward meeting the
Phase I objectives, demonstrating feasibility, and providing a solid
foundation for the proposed Phase II activity?
2. Did the applicant submit a concise Commercialization Plan (Product
Development Plan) that adequately addresses the areas described in the
Research Plan item J?
3. Does the project carry a high degree of commercial potential, as
described in the Commercialization Plan?
Amended Applications
In addition to the above criteria, the following criteria will be applied to
revised applications.
1. Are the responses to comments from the previous SRG review adequate?
2. Are the improvements in the revised application appropriate?
Phase I/Phase II Fast-Track Application Review Criteria
For Phase I/Phase II Fast Track applications, the following criteria also
will be applied:
1. Does the Phase I application specify clear, appropriate, measurable
goals (milestones) that should be achieved prior to initiating Phase
II?
2. Did the applicant submit a concise Commercialization Plan (Product
Development Plan) that adequately addresses the areas described in the
Research Plan, item J?
3. To what extent was the applicant able to obtain letters of interest,
additional funding commitments, and/or resources from the private
sector or non-SBIR/ STTR funding sources that would enhance the
likelihood for commercialization?
4. Does the project carry a high degree of commercial potential, as
described in the Commercialization Plan?
Phase I and Phase II Fast-Track applications that satisfy all of the review
criteria will receive a single rating. Failure to provide clear, measurable
goals may be sufficient reason for the scientific review group to exclude the
Phase II application from Fast-Track review.
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
PROTECTIONS: The adequacy of the proposed protection for humans, animals, or
the environment, to the extent they may be adversely affected by the project
proposed in the application.
INCLUSION: The adequacy of plans to include subjects from both genders, all
racial and ethnic groups (and subgroups), and children as appropriate for the
scientific goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria included in the
section on Federal Citations, below)
BUDGET: The appropriateness of the proposed budget and duration in relation
to the proposed research. The following evaluation criterion will be
presented in an administrative note in the Summary Statement and will not
factor into the numerical score:
DATA SHARING: The adequacy of plans to make the methods and materials
generated in the project widely available in a timely fashion to the
scientific community, given the proposed plan to exercise (or not to
exercise) intellectual property rights.
AWARD CRITERIA
Applications will compete for available funds with all other recommended SBIR
and STTR applications. Funding decisions for Phase I or Phase II applications
will be based on quality of the proposed project as determined by peer
review, availability of funds, and relevance to program priorities.
Phase II applications will be selected for funding based on the initial
priority score, assessment of the Phase I progress and determination that
Phase I goals were achieved, the project's potential for commercial success,
and the availability of funds.
FAST-TRACK Phase II applications may be funded following submission of the
Phase I progress report and other documents necessary for continuation.
REQUIRED FEDERAL CITATIONS
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components
involving Phase I and II clinical trials must include provisions for
assessment of patient eligibility and status, rigorous data management,
quality assurance, and auditing procedures. In addition, it is NIH policy
that all clinical trials require data and safety monitoring, with the method
and degree of monitoring being commensurate with the risks (NIH Policy for
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12,
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported
by the NIH, unless there are scientific and ethical reasons not to include
them. This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the inclusion of children as participants in
research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED
EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy
requires education on the protection of human subject participants for all
investigators submitting NIH proposals for research involving human subjects.
You will find this policy announcement in the NIH Guide for Grants and
Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide the official NIH
identifier(s)for the hESC line(s)to be used in the proposed research.
Applications that do not provide this information will be returned without
review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope of
this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore, we
caution reviewers that their anonymity may be compromised when they directly
access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This PA
is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.839 (NHLBI, DBDR), and No. 93.848 (NIDDK,
DKUHD) and is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review. Awards are made under
authorization of Sections 301 and 405 of the Public Health Service Act as
amended (15 USC 638 and 42 USC 241 and 284) and administered under NIH grants
policies described at http://grants.nih.gov/grants/policy/policy.htm and
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in
certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Weekly TOC for this Announcement
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